Mycobacterium Avium Complex Pulmonary Disease
Conditions
Keywords
Mycobacterium Avium Complex Pulmonary Disease, non-tuberculous mycobacterium, contezolid
Brief summary
The goal of this clinical trial is to learn if adding contezolid works to shorten the length of treatment in mycobacterium avium pulmonary disease in adults. It will also learn about the safety of extended usage of contezolid. The main questions it aims to answer are: Does adding contezolid to standard regimen decrease the bacterial load, lesion severity and improve the life quality of patients with mycobacterium avium pulmonary disease? What medical problems do participants have when taking contezolid for an extended length? Researchers will compare standard regimen plus contezolid to standard regimen alone to see if contezolid helps further decrease the bacterial load, lesion severity and improve the life quality of patients with mycobacterium avium pulmonary disease? Participants will: Take contezolid and standard regimen (azithromycin, ethambutol, and rifampicin) for 6 months, contezolid is administered every day while other drugs are taken three times a week OR take standard regimen three times a week for 12 months. Visit the clinic once every 1 month for checkups and tests.
Interventions
DRUGContezolid
contezolid 800mg po q12h\*6m
DRUGAzithromycin
azithromycin 500mg po tiw (250mg po tiw for BW under 50kg)\*6m
DRUGEthambutol (E)
ethambutol 25mg/kg po tiw\*6m
DRUGRifampicin (R)
rifampicin 600mg po tiw (450mg po tiw for BW under 50kg)\*6m
Sponsors
MicuRx
Shanghai Pulmonary Hospital, Shanghai, China
Beijing Chest Hospital
Anhui Chest Hospital
Jiangxi Chest Hospital
Guangzhou Chest Hospital.
Bin Cao
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients voluntarily participate in this study and sign the Informed Consent Form. 2. Age ≥ 18 years and ≤75 years; gender unrestricted. 3. Confirmed diagnosis of MAC pulmonary disease per ATS/IDSA 2020 guidelines or Chinese Guidelines for Diagnosis and Treatment of Nontuberculous Mycobacterial Diseases (2020 edition), with imaging features consistent with nodular bronchiectatic type. 4. No prior anti-MAC treatment within the 3 months preceding screening. 5. For premenopausal women of childbearing potential who are not surgically sterile: Must use a medically accepted contraceptive method (e.g., intrauterine device, hormonal contraception, or condom) during the study period and for 3 months following the last dose of investigational treatment. Serum or urine human chorionic gonadotropin (hCG) test must be negative within 72 hours prior to enrollment. Must not be breastfeeding. Male patients with partners of childbearing potential must use effective contraception during the study period and for 3 months after the last dose. 6. Organ function criteria met within one week prior to enrollment: i. Hemoglobin ≥60 g/L; ii. Neutrophil count ≥0.5 × 10⁹/L; iii. Platelet count ≥60 × 10⁹/L; iv. Serum total bilirubin ≤3 × upper limit of normal (ULN); v. Aspartate aminotransferase (AST) ≤3 × ULN; vi. Alanine aminotransferase (ALT) ≤3 × ULN; vii. Serum creatinine \<2 × ULN OR creatinine clearance ≥60 mL/min; viii. Blood urea nitrogen (BUN) ≤200 mg/L; ix. Urinalysis: Proteinuria \<++; if proteinuria is +, 24-hour total protein must be \<500 mg. x. Fasting blood glucose within normal range OR stable glycemic control in diabetic patients. xi. Cardiac function: No myocardial infarction in the preceding 6 months; No unstable angina or severe arrhythmias; New York Heart Association (NYHA) functional class \>II.
Exclusion criteria
1. History of allergy to any study drug in the treatment regimen. 2. Mixed infections with multiple mycobacteria, bacteria, fungi, or viruses (e.g., HIV coinfection). 3. Presence of congenital/acquired immunodeficiency disorders, active pulmonary malignancy (primary or metastatic), or other malignancies requiring chemotherapy/radiation therapy during the screening or study period. 4. History of solid organ transplantation. 5. Currently undergoing dialysis. 6. Uncontrolled radiation pneumonitis requiring steroid or immunoglobulin pulse therapy, active interstitial lung disease with clinical evidence, uncontrolled and significant pleural effusion or pericardial effusion. 7. Unstable systemic comorbidities including: Hypertensive crisis; Unstable angina; Congestive heart failure (NYHA Class III/IV); Myocardial infarction within the preceding 6 months; Severe psychiatric disorders requiring medication (e.g., schizophrenia, bipolar disorder); Severe hepatic or renal dysfunction (e.g., Child-Pugh Class C cirrhosis, eGFR \<30 mL/min/1.73m²); Neurodegenerative diseases (e.g., Alzheimer's disease). 8. Poor gastrointestinal function or malabsorption syndrome. 9. Receipt of other investigational drugs within 4 weeks prior to the first study drug administration. 10. Concurrent participation in another interventional clinical trial, unless it is an observational/noninterventional study OR follow-up phase of a completed intervention trial. 11. Any physical examination findings or clinical tests deemed by the investigator as likely to: Interfere with study results; Increase risks of complications during treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| culture conversion | end of month 6 | 2 consecutive negative sputum mycobacterial culture at least 4 weeks apart, or one negative bronchoalveolar lavage fluid culture/NGS. |
| QOL-B+NTM module | end of month 6 | Improvement greater than MID in at least 7 out of 12 domains in QOL-B with NTM-module (must include respiratory symptoms and NTM-PD symptoms) |
| CT lesion absorption | end of month 6 | \>30% decrease in lesion size or number of nodules measured on CT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SGRQ | up to month 12 | — |
| time to positivity of mycobacterium culture | up to month 12 | — |
| Questionnaire: Quality of life-bronchiectasis (QOL-B) and NTM module | up to month 12 | Improvement greater than minimal importance difference in at least 7 out of 12 domains in QOL-B with NTM module (must include respiratory symptoms and NTM-PD symptoms) |
| culture conversion | up to month 12 | 2 consecutive negative sputum mycobacterial culture at least 4 weeks apart, or one negative bronchoalveolar lavage fluid culture/NGS. |
| CT lesion status | end of month 3, 6, and 12 (for standard regimen)/end of month 3 and 6 (for shortened regimen) | \>30% decrease in lesion size or number of nodules measured on CT |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events | up to month 12 | Adverse events related to study intervention (short-term regimen and standard regimen) are reported by participants. |
| Number of participants with treatment-related abnormal laboratory tests results | up to month 12 | Laboratory tests include complete blood count, liver function and kidney function. Abnormalities will be recorded and discussed to determine the causality between treatment and laboratory findings. |
| MAC strain drug-sensitivity | end of month 6 (for shortened regimen)/end of month 12 (for standard regimen) | Phenotypic drug sensitivity will be evaluated with microdilution method for macrolides, amikacin, rifampicin, and ethanmbutol |
Countries
China
Contacts
Primary ContactSiwei Gu, M.D.
Outcome results
None listed